• My research goal is to better understand the biochemical mechanisms that facilitate chemoresistance and employ NMR spectroscopy and synthetic peptides to identify novel therapeutic targets to suppress chemoresistance. To this end, my research focuses on two primary avenues: 1) Characterization of rBH3 motif mediated regulation of anti-apoptotic Bcl-2 family members; 2) Development of targeted inhibitors of the SUMOylation E2 enzyme, Ubc9. We also employ our expertise in peptide synthesis and assay design to develop peptide-based high-throughput screening assays that are amenable for small-molecule drug discovery and in the development of first-in-class peptide inhibitors that can be used to validate new therapeutic targets in cancer.
  • Selected Publications

    Academic Article

    Year Title Altmetric
    2021 The multiple mechanisms of MCL1 in the regulation of cell fateCommunications Biology.  4. 2021
    2020 A cell-penetrating MARCKS mimetic selectively triggers cytolytic death in glioblastomaOncogene.  39:6961-6974. 2020
    2020 MCL1 binds and negatively regulates the transcriptional function of tumor suppressor p73Cell Death and Disease.  11. 2020
    2020 The GTPase Rab27b regulates the release, autophagic clearance, and toxicity of alpha-synucleinJournal of Biological Chemistry.  295:8005-8016. 2020
    2020 MCL1 binding to the reverse BH3 motif of P18INK4C couples cell survival to cell proliferationCell Death and Disease.  11. 2020
    2020 Novel EGFR ectodomain mutations associated with ligand-independent activation and cetuximab resistance in head and neck cancerPLoS ONE.  15. 2020
    2019 Specific inhibition of DPY30 activity by ASH2L-derived peptides suppresses blood cancer cell growthExperimental Cell Research.  382. 2019
    2019 IgA1 hinge-region clustered glycan fidelity is established early during semi-ordered glycosylation by GalNAc-T2Glycobiology.  29:543-556. 2019
    2019 Regulating the bcl2 family to improve sensitivity to microtubule targeting agentsCells.  8. 2019
    2019 UBC9 Mutant Reveals the Impact of Protein Dynamics on Substrate Selectivity and SUMO Chain LinkagesBiochemistry.  58:621-632. 2019
    2018 14-3-3 proteins reduce cell-to-cell transfer and propagation of pathogenic α-synuclein 2018
    2018 PTBP1 enhances miR-101-guided AGO2 targeting to MCL1 and promotes miR-101-induced apoptosis articleCell Death and Disease.  9. 2018
    2018 Post-transcriptional regulation of anti-apoptotic BCL2 family membersInternational Journal of Molecular Sciences.  19. 2018
    2018 Serum galactose-deficient-IgA1 and IgG autoantibodies correlate in patients with IgA nephropathyPLoS ONE.  13. 2018
    2016 PTBP1 modulation of MCL1 expression regulates cellular apoptosis induced by antitubulin chemotherapeuticsCell Death and Differentiation.  23:1681-1690. 2016
    2013 Erratum to The E3Ubiquitin Ligase Siah2 Contributes to Castration-Resistant Prostate Cancer by Regulation of Androgen Receptor Transcriptional Activity [Cancer Cell 23, (2013) 332-346]Cancer Cell.  23:853. 2013
    2013 The E3 ubiquitin ligase siah2 contributes to castration-resistant prostate cancer by regulation of androgen receptor transcriptional activityCancer Cell.  23:332-346. 2013
    2012 Novel targeted system to deliver chemotherapeutic drugs to EphA2-expressing cancer cellsJournal of Medicinal Chemistry.  55:2427-2436. 2012
    2012 Sabutoclax, a Mcl-1 antagonist, inhibits tumorigenesis in transgenic mouse and human xenograft models of prostate cancerNeoplasia.  14:656-665. 2012
    2011 An optically pure apogossypolone derivative as potent pan-active inhibitor of anti-apoptotic Bcl-2 family proteinsFrontiers in Oncology.  1. 2011
    2011 Identification of a novel Mcl-1 protein binding motifJournal of Biological Chemistry.  286:39829-39835. 2011
    2010 Synthesis and biological evaluation of apogossypolone derivatives as pan-active inhibitors of antiapoptotic B-cell lymphoma/leukemia-2 (Bcl-2) family proteinsJournal of Medicinal Chemistry.  53:8000-8011. 2010
    2010 BI-97C1, an optically pure apogossypol derivative as pan-active inhibitor of antiapoptotic B-cell lymphoma/Leukemia-2 (Bcl-2) family proteinsJournal of Medicinal Chemistry.  53:4166-4176. 2010
    2010 A survey of the anti-apoptotic Bcl-2 subfamily expression in cancer types provides a platform to predict the efficacy of Bcl-2 antagonists in cancer therapyCell Death and Disease.  1. 2010
    2007 Cold-adaptation in Sea-water-borne Signal Proteins: Sequence and NMR Structure of the Pheromone En-6 from the Antarctic Ciliate Euplotes nobiliiJournal of Molecular Biology.  372:277-286. 2007
    2007 Cold-adapted signal proteins: NMR structures of pheromones from the antarctic ciliate Euplotes nobilii 2007
    2007 NMR Solution Structure of the Pheromone En-1 2007
    2007 NMR Structure and Functional Characterization of a Human Cancer-related Nucleoside TriphosphataseJournal of Molecular Biology.  367:788-801. 2007
    2006 NMR assignment of a human cancer-related nucleoside triphosphatase [57]Journal of Biomolecular NMR.  36:59. 2006
    2006 Solution structures of the putative anti-σ-factor antagonist TM1442 from Thermotoga maritima in the free and phosphorylated statesMagnetic Resonance in Chemistry.  44. 2006
    2005 Volatile anesthetics bind rat synaptic snare proteinsAnesthesiology.  103:768-778. 2005
    2002 Volatile Anesthetics Bind to Synaptic SNARE Proteins and the SNARE ComplexAnesthesiology.  96:A813-A813. 2002
    Rab27b regulates the release, autophagic clearance, and toxicity of alpha-synuclein

    Research Overview

  • Current projects being pursued in the lab are:
    1. Characterizing the impact that reverse BH3 (rBH3)-containing proteins have on regulation of the anti-apoptotic Bcl-2 family proteins, especially MCL-1.

    2. Determining the post-transcriptional regulators of the anti-apoptotic Bcl-2 family protein MCL-1.

    3. Utilizing mutants of the SUMO E2 ligase, Ubc9, to study the structural determinants of SUMO target selection.

    4. Developing high-throughput screening assays for use in anti-cancer therapeutic development.
  • Education And Training

  • Sanford-Burnham Medical Research Institute, Postdoctoral Fellowship
  • Doctor of Philosophy in Molecular Biology, The Scripps Research Institute 2007
  • Full Name

  • William Placzek